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Your search keyword '"Trikha, Mohit"' showing total 23 results
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23 results on '"Trikha, Mohit"'

13. Marizomib for central nervous system-multiple myeloma.

Author

Badros, Ashraf, Singh, Zeba, Dhakal, Binod, Kwok, Young, MacLaren, Ann, Richardson, Paul, Trikha, Mohit, and Hari, Parameswaran

Subjects
PROTEASOME inhibitors, MULTIPLE myeloma treatment, TREATMENT of central nervous system cancer, GLIOMA treatment, NATURAL products, POSITRON emission tomography, DRUG efficacy, THERAPEUTICS
Abstract

Marizomib, a natural marine product, is an irreversible proteasome inhibitor currently under investigation in relapsed-refractory multiple myeloma ( RRMM) and malignant glioma. Central nervous system-multiple myeloma ( CNS- MM) is a rare manifestation of extra-medullary disease with few therapeutic options, highlighting the unmet clinical need in these patients. Marizomib demonstrated encouraging activity in RRMM and has emerging clinical activity in glioma, making it a potential CNS- MM therapeutic intervention. Herein, we present two patients with RRMM and CNS involvement who benefited from marizomib-based therapy. These cases provide the first proof of principle for further exploring marizomib in CNS- MM patients. [ABSTRACT FROM AUTHOR]

Published
2017
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15. Marizomib irreversibly inhibits proteasome to overcome compensatory hyperactivation in multiple myeloma and solid tumour patients.

Author

Levin, Nancy, Spencer, Andrew, Harrison, Simon J., Chauhan, Dharminder, Burrows, Francis J., Anderson, Kenneth C., Reich, Steven D., Richardson, Paul G., and Trikha, Mohit

Subjects
MULTIPLE myeloma treatment, PROTEASOME inhibitors, TUMORS, CHYMOTRYPSIN, PHARMACODYNAMICS
Abstract

Proteasome inhibitors ( PIs) are highly active in multiple myeloma ( MM) but resistance is commonly observed. All clinical stage PIs effectively inhibit chymotrypsin-like ( CT-L) activity; one possible mechanism of resistance is compensatory hyperactivation of caspase-like (C-L) and trypsin-like (T-L) subunits, in response to CT-L blockade. Marizomib ( MRZ), an irreversible PI that potently inhibits all three 20S proteasome subunits with a specificity distinct from other PIs, is currently in development for treatment of MM and malignant glioma. The pan-proteasome pharmacodynamic activity in packed whole blood and peripheral blood mononuclear cells was measured in two studies in patients with advanced solid tumours and haematological malignancies. Functional inhibition of all proteasome subunits was achieved with once- or twice-weekly MRZ dosing; 100% inhibition of CT-L was frequently achieved within one cycle at therapeutic doses. Concomitantly, C-L and T-L activities were either unaffected or increased, suggesting compensatory hyperactivation of these subunits. Importantly, this response was overcome by continued administration of MRZ, with robust inhibition of T-L and C-L (up to 80% and 50%, respectively) by the end of Cycle 2 and maintained thereafter. This enhanced proteasome inhibition was independent of tumour type and may underlie the clinical activity of MRZ in patients resistant to other PIs. [ABSTRACT FROM AUTHOR]

Published
2016
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